Dysregulated Diurnal Cortisol Pattern and Heightened Night-Time Cortisol in Individuals with Bipolar Disorder.

INTRODUCTION: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may contribute to the symptom burden in bipolar disorder (BD). Further characterization of cortisol secretion is needed to improve understanding of the connection between mood, sleep, and the HPA axis. Here, we observe diurnal cortisol patterns in individuals with BD and healthy controls (HCs) to determine time points where differences may occur. METHODS: Salivary cortisol was measured at 6 time points (wake, 15, 30, and 45 min after wake, between 2:00 and 4:00 p.m. and 10:00 p.m.) for 3 consecutive days in individuals with symptomatic BD (N = 27) and HC participants (N = 31). A general linear model with correlated errors was utilized to determine if salivary cortisol changed differently throughout the day between the 2 study groups. RESULTS: A significant interaction (F = 2.74, df = 5, and p = 0.02) was observed between the time of day and the study group (BD vs. HC) when modeling salivary cortisol over time, indicating that salivary cortisol levels throughout the day significantly differed between the study groups. Specifically, salivary cortisol in BD was elevated compared to HCs at the 10:00 p.m. time point (p = 0.01). CONCLUSION: Significantly higher levels of cortisol in participants with BD in the night-time suggest that the attenuation of cortisol observed in healthy individuals may be impaired in those with BD. Reregulation of cortisol levels may be a target of further study and treatment intervention for individuals with BD.

Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder.

BACKGROUND: Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. METHOD: This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2-19), and following (Study Days 20-21) residential treatment. DISCUSSION: This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . PROTOCOL VERSION: 10 May 2023.

Effects of trazodone versus cognitive behavioral therapy in the insomnia with short sleep duration phenotype: a preliminary study.

STUDY OBJECTIVES: The insomnia with objective short sleep duration phenotype is associated with increased risk for adverse health outcomes, physiological hyperarousal, and a blunted response to cognitive behavioral therapy for insomnia (CBT-I). Whether insomnia with objective short sleep duration responds better to pharmacological treatment compared to CBT-I has not been examined. METHODS: Participants included 15 patients with chronic insomnia (86.7% female), aged 45.3 ± 8.1 years. Eight patients were randomized to CBT-I and 7 to trazodone. Patients were examined with 2 weeks of actigraphy, salivary cortisol, and the insomnia severity index at 3 time points (pretreatment, 3-month posttreatment, and 6-month follow-up). Mixed between-within-subjects analysis of variance and univariate analysis of covariance were conducted to assess the impact of trazodone and CBT-I on patients' total sleep time, salivary cortisol, and insomnia severity index scores across the 3 time points. RESULTS: Trazodone, but not CBT-I, significantly lengthened total sleep time (when measured with actigraphy) both at posttreatment (51.01 minutes vs -11.73 minutes; P = .051; Cohen's d = 1.383) and at follow-up (50.35 minutes vs -7.56 minutes; P = .012; Cohen's d = 1.725), respectively. In addition, trazodone, but not CBT-I, showed a clinically meaningful decrease in salivary cortisol from pretreatment to posttreatment (-36.07% vs -11.70%; Cohen's d = 0.793) and from pretreatment to follow-up (-21.37% vs -5.79%; Cohen's d = 0.284), respectively. Finally, there were no differences on insomnia severity index scores between the trazodone and the CBT-I groups. CONCLUSIONS: The current preliminary, open-label, randomized trial suggests that trazodone, but not CBT-I, significantly improves objective sleep duration and reduces hypothalamic-pituitary-adrenal axis activation, suggesting a differential treatment response in the insomnia with objective short sleep duration phenotype. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Study of Trazodone & Cognitive Behavioral Therapy to Treat Insomnia; URL: https://clinicaltrials.gov/ct2/show/NCT01348542; Identifier: NCT01348542.

Use of ecological momentary assessment to detect variability in mood, sleep and stress in bipolar disorder.

OBJECTIVE: Our aim was to study within-person variability in mood, cognition, energy, and impulsivity measured in an Ecological Momentary Assessment paradigm in bipolar disorder by using modern statistical techniques. Exploratory analyses tested the relationship between bipolar disorder symptoms and hours of sleep, and levels of pain, social and task-based stress. We report an analysis of data from a two-arm, parallel group study (bipolar disorder group N = 10 and healthy control group N = 10, with 70% completion rate of 14-day surveys). Surveys of bipolar disorder symptoms, social stressors and sleep hours were completed on a smartphone at unexpected times in an Ecological Momentary Assessment paradigm twice a day. Multi-level models adjusted for potential subject heterogeneity were adopted to test the difference between the bipolar disorder and health control groups. RESULTS: Within-person variability of mood, energy, speed of thoughts, impulsivity, pain and perception of skill of tasks was significantly higher in the bipolar disorder group compared to health controls. Elevated bipolar disorder symptom domains in the evening were associated with reduced sleep time that night. Stressors were associated with worsening of bipolar disorder symptoms. Detection of symptoms when an individual is experiencing difficulty allows personalized, focused interventions.

"What's in a name?" Delirium by any other name would be as deadly. A review of the nature of delirium consultations.

INTRODUCTION: Delirium is often underdiagnosed, resulting in adverse clinical outcomes. The goal of this study was to identify how patients correctly diagnosed with delirium differ from those who are misdiagnosed. METHODS: A retrospective chart review was conducted using a database of 1,000 consecutive psychiatric consultation requests. Patients were identified based on a diagnosis of delirium made by the consultation team. Charts were then reviewed for data on race, gender, age, time and month of the consultation, documented diagnosis of mental illness, and information that would help establish a delirium diagnosis based on DSM-IV-TR criteria. Univariate and multivariate analyses were performed. RESULTS: Cases were judged to be diagnostically concordant (consultation requested for delirium or encephalopathy, n = 30) or discordant (n = 81). The two groups did not differ significantly in age, sex, race, time and month of the consultation, or documentation of mental illness. The concordant group had a significantly greater number of identifiable diagnostic criteria compared to the discordant group (mean 3.0 ± 0.8 criteria vs. 1.9 ± 1.3 criteria, P < 0.001). Identification of individual diagnostic criteria was greater in the concordant group, with significant differences for two of four categories, namely acute onset (100.0% vs. 50.6%, P < 0.001) and fluctuating course (93.3% vs. 66.7%, P = 0.004). Multivariate analysis suggested increased odds of identifying delirium if more diagnostic criteria were identifiable (OR: 2.355, P < 0.001, confidence interval [CI] 1.502-3.690), and increased likelihood of the delirium diagnosis being missed if there was documentation of psychiatric illness (OR: 0.387, P = 0.049, CI: 0.151-0.995). CONCLUSION: This study highlights the need for educational programs and easy to implement screening tools to ensure delirium is not overlooked.